Process for producing 3-cyanomethyl cyclopentanone derivatives

ABSTRACT

A process for producing 3-cyanomethyl cyclopentanone derivatives which are useful precursors of fragrant components in jasmine and analogous thereof such as methyl jasmonoate, methyl dihydrojasmonate, etc., is disclosed. In the process, the jasmonoates are produced starting from β-dicarbonyl compounds and azides through several-step reactions.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part of application Ser. No.661,263, filed Feb. 25, 1976.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to a novel process for producing3-cyanomethyl cyclopentanone derivatives which are useful precursors offragrant components such as methyl jasmonoate, methyl dihydrojasmonate,etc.

2. Description of the Prior Art

The 3-cyanomethyl cyclopentanone derivatives having the formula ##STR1##wherein R¹ represents hydrogen atom or an alkyl group, an alkenyl groupor an alkynyl group and R² represents hydrogen atom, an alkoxycarbonylgroup or an acyl group are useful as the precursor of jasmonoides whichmean the fragrant components in jasmine and analogous thereof, such asmethyl jasmonoate, methyl dihydrojasmonate, etc. which impart thecharacteristic fragrances of jasmine [E. H. Polak, Cosmetics andPerfumery, 88, 46 (1973)]. These compounds have also been considered tobe important as fragrant reinforcing substances.

Various processes for producing jasmonoids have been reported. [T. L.Ho. Syn. Commun., 4, 265 (1974)], for example, the synthesis of methyljasmonoate from cyclopentanonenamine derivatives [E. Demole, et al.,Helv. Chem. Acta, 45, 692 (1962)]; the process for reacting aneucleophilic reagent with a cyclopentanone derivative [G Buchi, et al.,J. Org. Chem 36, 2021 (1971); A I Meyers, et al., J Org. Chem. 38, 175(1973); A. E. Greene, et al., Tetrahedron Lett., 4867 (1976)], thesynthesis from indanone derivatives [S. Torii et al., J. Org. Chem. 40,462 (1975)], the process for using an intermediate obtained by anelectrolysis of a norbornane derivative [S. Torii et al., J Org Chem.40, 2221 (1975)].

These processes respectively have disadvantages that the startingmaterials are not easily obtained, the selectivity of the reaction islow in some cases, the reaction steps are lengthy, the expensive reagentis needed in some cases, the operation in the reaction is not easy, etc.

The inventors have studied the process for producing jasmonoids inindustrial operation and have found the process for easily producing the3-cyanomethyl cyclopentanone derivative having the formula (VI) which isuseful as the precursor of the jasmonoids.

SUMMARY OF THE INVENTION

It is an object of the present invention to provide a process forproducing 3-cyanomethyl cyclopentanone derivatives which are useful asthe precursor of the jasmonoids by a simple industrial process.

The process of the present invention is summarized by the followingreaction scheme: ##STR2## wherein R¹ represents hydrogen atoms, an alkylgroup, an alkenyl group or an alkynyl group and R³ represents an alkoxygroup or an alkyl group.

DETAILED DESCRIPTION OF THE EMBODIMENTS

Each step of the synthetic scheme will be illustrated in more detail. Itshould be noted that the compounds are shown by the typicalnomenclature, for example, pentanoic acid (C₄ H₉ COOH) andcyclopentanecarboxylic acid (C₅ H₉ COOH).

In the Step I reaction, the β-dicarbonyl compounds having the formula##STR3## (R³ is defined above) which are the starting material in StepI, can easily be produced by the condensation reaction of acetoaceticacid esters or acetylacetones with alkylhalides (as shown inReferences).

The typical compounds having the formula (I) include β-ketoesters suchas 3-oxo-6-heptenoic acid esters; and β-diketones such as7-octene-2,4-dione and 8-nonene-3,5-dione. The Step I comprises areaction of the β-dicarbonyl compound (I) with an azide.

The azides can be tosyl azide, benzenesulfonyl azide, phenyl azide,azidoformic acid esters and other various azides.

The reaction of the Step I should be conducted under basic condition.The basic condition can be attained by an addition of alkali metalhydroxides such as sodium hydroxide and potassium hydroxide; alkalimetal alkoxides such as sodium methoxide, sodium ethoxide, sodiumt-butoxide, potassium t-butoxide; and organic amines such astriethylamine, tributylamine, dimethylaniline, pyridine and piperidinein the reaction system: The necessary amount of the base is preferablyabout equimole to the starting materials.

In the operation of the Step I, the reaction can be conducted withoutusing a solvent. However in order to increase the yield of the productunder mild reaction condition, it is preferable to use a solvent such asacetonitrile, dimethylformamide, tetrahydrofuran, alcohols, ethers,methylene chloride and the like.

When the operation of the Step I is conducted under the said condition,the reaction can smoothly be performed without specific heating orcooling of the system to produce α-diazo-β-dicarbonyl compounds.

The typical α-diazo-β-dicarbonyl compounds having the formula (II)##STR4## (R³ is defined above) which are produced by the operation ofthe Step (I) include α-diazo-β-ketoesters such as3-oxo-2-diazo-6-heptenoic acid esters, and α-diazo-β-diketones such as7-octene-3-diazo-2,4-dione, 8-nonene-4-diazo-3,5-dione and the like.

In the Step II, it is necessary to subject α-diazo-β-dicarbonylcompounds having the formula (II) to the condition which enable theformation of carbene or carbenoid.

The carbene or carbenoid forming condition can be attained by (1)treatment with a catalyst or (2) photoirradiation.

In the catalyzed decomposition method, a trace amount of catalyst suchas metals or metal salts e.g. copper powder, copper bronze, copperhalides, cupper sulfate, copper acetylacetonate, copper-phosphinecomplex, silver oxide, silver nitrate and the like, is used in an inertatmosphere to form carbenoids.

In the photodecomposing method, the compound (II) is directly irradiatedor irradiated in an inert atmosphere to form carbenes. The conventionallight sources used in photochemical industries such as a low pressuremercury lamp as well as high pressure mercury lamp can be used as thelight source.

It is not always necessary to use a solvent in either the catalyticmethod or the photodecomposing method. However, in order to avoid theformation of by-product and to obtain the desired compound in high yieldand selectivity, it is preferable to conduct it in an inert medium. Theconditions of the inert medium can be attained by conducting thereaction under an inert atmosphere, such as nitrogen or argon gas andusing the solvent such as benzene, toluene, xylene, hexane, petroleumether and the like, as the reaction medium.

The carbenes or carbenoids formed under the said conditions immediatelyand selectively result in acyclo-addition to the unsaturated double bondof the same molecule to produce bicyclo [3.1.0] hexan-2-one derivativesin high yield.

The bicyclo compounds produced by the Step II reaction, have electronwithdrawing substituent at 1-position.

Accordingly, it makes easy to cleave the cyclopropane ring by the attackof nucleophile as shown in the next step reaction and the substituentalso controls the direction of ring cleavage. In other words, as aresult of having this substituent at 1-position, one of the threecarbon-carbon bonds of the cyclopropane ring can selectively be cleavedto produce cyclopentanone derivatives.

The typical bicyclo [3.1.0] hexan-2-one derivatives having the formula(III) ##STR5## (R³ is defined above) which are produced by the Step II,include 2-oxo-bicyclo [3.1.0] hexane-1-carboxylic acid esters,1-acetyl-bicyclo [3.1.0] hexan-2-one, 1-propionyl-bicyclo [3.1.0]hexan-2-one and the like.

In the Step III reaction, it is necessary to react the bicyclo [3.1.0]hexan-2-one derivative having the formula (III) with a cyanating reagentin an alkaline condition.

The typical cyanating reagents include hydrogen cyanide, acetonecyanohydrin and metal cyanides such as potassium cyanide, sodiumcyanide, copper cyanide, mercury cyanide, aluminum cyanide, etc..

It is necessary to carry out the reaction under basic condition. When analkali metal cyanide is used, the basic condition can be attained by theaddition of the alkali metal cyanide. Accordingly, it is unnecessary toadd the other alkaline compound.

When hydrogen cyanide is used, the basic condition can be attained byadding a base such as sodium hydroxide, potassium hydroxide, sodiumcarbonate, potassium carbonate, triethylamine, pyridine, etc..

It is preferable to carry out the reaction in an inert solvent such asalcohols, ethers and dimethylformamide, N-methylpyrrolidone,acetonitrile, dimethyl sulfoxide, hexamethylphosphoric triamide, etc.

The reaction can be smoothly performed at the room temperature withoutusing a special heating means or a cooling means.

It is considered that the reaction mechanism using a metal cyanide is asfollows. ##STR6##

As shown in the reaction formula, a partial ring cleavage of the bicycloring of the Compound (III) is carried out by the attack of CN anions ofthe cyanating reagent to form the anionic active compound and then, thecompound is converted to the Compound (IV) by an acid treatment.

In the Step IV reaction, an alkylation is selectively carried out at1-position of 5-cyanomethyl-2-oxo-cyclopentanecarboxylic acid ester.

The alkylating agents have the formula

    R.sup.1 Z

wherein R¹ represents an alkyl group, an alkenyl group or an alkynylgroup and Z represents a halogen atom, tosyloxy group or acyloxy group.

The reaction is carried out in the presence of a base such as alkalimetal carbonates, alkali metal hydroxides, alkali metal alkoxides,alkali metal hydrides, organic amines.

It is preferable to use a solvent such as alcohols, ethers,hydrocarbons, polar solvents e.g. dimethyl sulfoxide,hexamethylphosphoric triamide, etc.

In the Step V reaction, an alkoxycarbonyl group or acyl group at1-position of 5-cyanomethyl-2-oxo-cyclopentane having the formula (IV)or (V) is eliminated by hydrolyzing it and then heating the hydrolyzedproduct or by heating it in the presence of an alkali metal salt.

The 3-cyanomethylcyclopentanone having the formula (VI) wherein both R¹and R² are hydrogen atoms, is obtained from the Compound (IV).

The 3-cyanomethylcyclopentanone derivative having the formula (VI)wherein R² is hydrogen atom and R¹ is the corresponding substituent isobtained from the Compound (V).

These 3-cyanomethylcyclopentanone derivatives having the formula (IV),(V) and (VI) are precursors of jasmonoides.

Preparation 1

A solution of p-toluenesulfonyl azide (592 mg, 3 mmol) in 1 ml ofacetonitrile was added at room temperature to a solution of3-oxo-6-heptenoic acid methyl ester (468 mg, 3mmol) and triethylamine(306 mg, 3 mmol) in 5 ml of acetonitrile.

The mixture was stirred for about 2 hours and the solvent was distilledoff under a reduced pressure and the product was dissolved in with 50 mlof ether.

The solution was washed with 5% aqueous solution of potassium hydroxideuntil no color of the aqueous phase was found and was further washedwith a saturated aqueous solution of sodium chloride.

The ether solution was dried over anhydrous magnesium sulfate and wasfiltered and condensed under a reduced pressure to obtain 530 mg of2-diazo-3-oxo-6-heptenoic acid methyl ester as yellow oily product. Thecrude product can be purified by the distillation under a reducedpressure. Yield: 97%. Boiling point: 67 - 68° C/0.4 mmHg. Infraredspectrum (cm⁻¹): 2120, 1725, 1655. NMR spectrum (CCl₄) δ : 3.77 (s, 3H),4.65 - 5.20 (m, 2H), 5.47 - 6.13 (m, 1H).

Preparation 2

In argon atmosphere, the unpurified 2-diazo-3-oxo-6-heptenoic acidmethyl ester of Preparation 1 (4.55 g, 25 mmol) was dissolved in 100 mlof benzene.

An anhydrous cupric sulfate (2.5 g) was added as a catalyst to thesolution.

The mixture was stirred for about 3 hours under refluxing. Afterconfirming the disappearance of the starting materials by a thin layerchromatography, the reaction mixture was filtered through Celite column.

The solvent was distilled off from the filtrate under a reduced pressureand the remained oily product was distilled under a reduced pressure toobtain 2.92 g of 2-oxo-bicyclo [3.1.0] hexane-1-carboxylic acid methylester as oily product. Yield: 69% based on methyl 3-oxo-6-heptenoate.Boiling point: 90° C/0.7 mmHg. NMR spectrum (CCl₄) δ : 1.33 t, J=5Hz,1H), 1.77 - 2.30 (m, 4H), 2.30 - 2.73 (m, 2H), 3.68 (s, 3H). Massspectrum(m/e %) : 154 (55), 126 (87), 123 (56), 113 (94), 67 (62), 66(54), 59 (75). Infrared spectrum (cm⁻¹) : 1755, 1725.

Preparation 3

In argon atmosphere, 2-diazo-3-oxo-6-heptenoic acid methyl ester (34 g,0.187 mmol) was dissolved in benzene (300 ml). An acetyl acetone-coppercomplex (1 g) was added to the solution. The mixture was stirred for onenight under refluxing. After cooling it, the solvent was distilled offunder a reduced pressure. The residue was purified by a distillation toobtain 17.1 g of 2-oxo-bicyclo [3.1.0] hexane-1-carboxylic acid methylester. Yield: 60%. Boiling point: 83° to 85° C/0.3 mmHg.

Preparation 4

In argon atmosphere, potassium cyanide (290 g, 44 mmol) and2-oxo-bicyclo [3.1.0] hexane-1-carboxylic acid methyl ester (6.18 g, 40mmol) was added to dimethyl sulfoxide (15 ml). The mixture was stirredat the room temperature for about three days and was acidified with adiluted hydrochloric acid. The reaction product was extracted with ethylacetate and dried over anhydrous magnesium sulfate and was concentrated.The residue (7.24 g) was purified by a silica gel column chromatography(ethyl acetate: n-hexane=2 : 3) to obtain an oily product.

The product was recrystallized from ethyl acetate and n-hexane to obtain5-cyanomethyl-2-oxo-cyclopentanecarboxylic acid methyl ester (4.7 g).Yield: 65%. Melting point: 49° to 50° C Infrared spectrum (cm⁻¹) : 2250,1755, 1725. NMR spectrum (CDCl₃) δ : 2.10 to 3.35 (m, 8H), 3.80 (s, 3H).Mass spectrum m/e : 181, 141, 109.

Preparation 5

5-Cyanomethyl-2-oxo-cyclopentanecarboxylic acid methyl ester (362 mg, 2mmol), lithium iodide (350 mg, 2.6 mmol) were dissolved indimethylformamide (3 ml).

The mixture was heated at 120 C with stirring. After 5 hours, thereaction mixture was cooled and admixed with an aqueous solution ofammonium chloride and the reaction product was extracted wth ethylacetate. The extract was washed with a saturated sodium chloride aqueoussolution and was dried over anhydrous magnesium sulfate and wasfiltered. The filtrate was concentrated under a reduced pressure. Theresidue was purified by a silica gel column chromatography (ethylacetate: n-hexane=3 : 7) to obtain 148 mg of 3-cyanomethylcyclopentanoneas oily product. Yield: 60%. Infrared spectrum (cm⁻¹): 2240, 1740. Massspectrum m/e : 123, 83, 55, 41.

Preparation 6

In argon atmosphere, sodium cyanide (200 mg, 4 mmol) and 2-oxo-bicyclo[3.1.0] hexane-1-carboxylic acid methyl ester (462 mg, 3 mmol) wereadded to dimethyl sulfoxide (2ml). The mixture was stirred at the roomtemperature for one night and was treated in accordance with the processof Preparation 4 to obtain 328 mg of5-cyanomethyl-2-oxo-cyclopentanecarboxylic acid methyl ester. Yield:60%.

Preparation 7

In argon atmosphere, potassium cyanide (260 mg, 4 mmol) and2-oxo-bicyclo [3.1.0] hexane-1-carboxylic acid methyl ester (462 mg, 3mmol) were added to hexamethylphosphoric triamide (3 ml). The mixturewas stirred at the room temperature for 24 hours and was treated inaccordance with the process of Preparation 4 to obtain 300 mg of5-cyanomethyl-2-oxo-cyclopentanecarboxylic acid methyl ester. Yield:55%.

Preparation 8

In argon atmosphere, potassium cyanide (260 mg, 4 mmol) and2-oxo-bicyclo [3.1.0] hexane-1-carboxylic acid methyl ester (462 mg, 3mmol) were added to dimethylformamide (3 ml). The mixture was stirred atthe room temperature for 24 hours and was treated in accordance with theprocess of Preparation 4 to obtain 290 mg of5-cyanomethyl-2-oxo-cyclopentanecarboxylic acid methyl ester. Yield:53%.

Preparation 9

3-Cyanomethyl-2-oxo-cyclopentanecarboxylic acid methyl ester (4.17 g, 23mmol) and 1-bromo-2-pentyne (4.06 g, 27.5 mmol) were dissolved inacetone (40 ml).

Potassium carbonate (3.19 g, 23 mmol) was added to the solution. Themixture was heated under refluxing with vigorously stirring for onenight. After cooling the reaction mixture, the solvent was distilled offunder a reduced pressure.

The residue was admixed with water and the reaction product wasextracted with ethyl acetate and was dried over anhydrous magnesiumsulfate and then the solvent was distilled off under a reduced pressure.

The residue was recrystallized from ethyl acetate and n-hexane to obtain2.77 g of 5-cyanomethyl-2-oxo-1-(2'-pentynyl)-cyclopentanecarboxylicacid methyl ester as white crystals. Yield: 49%. Melting point: 100 to101° C. Infrared spectrum (cm⁻¹) : 2250, 1753, 1730. NMR spectrum(DCCl₃) δ : 1.08 (t, J=6.5Hz, 3H), 1.90 - 3.09 (m, 11H), 3.67(s, 3H).Mass spectrum(m/e) : 247, 216, 188.

Preparation 10

5-Cyanomethyl-2-oxo-cyclopentanecarboxylic acid methyl ester (543 mg, 3mmol) and 1-bromo-2-pentyne (485 mg, 3.3 mmol) were dissolved in acetone(15 ml). Potassium carbonate (415 mg, 3 mmol) was added to the solution.The mixture was heated under refluxing with vigorously stirring for onenight. After cooling the reaction mixture, the solvent was distilled offunder a reduced pressure. The residue was directly purified by a silicagel column chromatography (ethyl acetate: n-hexane=1 : 4) to obtain 630mg of 5-cyanomethyl-2-oxo-1-(2'-pentynyl)-cyclopentanecarboxylic acidmethyl ester as white crystals. Yield: 85%

Preparation 11

5-Cyanomethyl-2-oxo-1-(2'-pentynyl)-cyclopentane carboxylic acid methylester (4.94 g, 20 mmol) was dissolved in dimethyl sulfoxide (10 ml).Lithium iodide (5.36 g, 40 mmol) was added to the solution with stirringand the mixture was stirred at 130° C for 3 hours and was cooled to theroom temperature.

The reaction mixture was purified by a silica gel column chromatography(ethyl acetate: n-hexane=3 : 7) to obtain 3.2 g of3-cyanomethyl-2-(2'-pentynyl)-cyclopentanone as oily product. Yield:85%.

Preparation 12

3-Cyanomethyl-2-(2'-pentynyl)-cyclopentanone (378 mg, 2 mmol) wasdissolved in anhdydrous methanol (10 ml). Lindlar catalyst (240 mg) wasadded to the solution. Hydrogen (49 ml) was fed into the mixture. Afterhydrogen addition, the reaction mixture was concentrated and the residuewas purified by a silica gel column chromatography (ethyl acetate:n-hexane=1 : 4) to obtain3-cyanomethyl-2-(cis-2'-pentenyl)-cyclopentanone (275 mg) as oilyproduct. Yield: 72%. Infrared spectrum (cm⁻¹) : 2248, 1745. NMR spectrum(CDCl₃) δ : 0.97 (t, J=7Hz, 3H), 1.52 - 3.00 (m, 12H), 4.95 - 5.80 (m,2H).

Preparation 13

3-Cyanomethyl-2-(2'-pentynyl)-cyclopentanone (2.49 g, 13.2 mmol) wasdissolved in anhydrous methanol (25 ml). Freshly prepared Lindlarcatalyst (750 mg) was added to the solution. Hydrogen (323 ml) was fedover the mixture. After the check of the completion of the equimolarhydrogen absorption by gas chromatography, the reaction mixture wasfiltered through Celite layer. The filtrate was concentrated under areduced pressure and the residue was distilled to obtain 2.28 g of3-cyanomethyl-2-(cis-2'-pentenyl)-cyclopentanone. Yield: 90% Boilingpoint: 126°-130° C/1.0 mmHg

Preparation 14

5-Cyanomethyl-2-oxo-cyclopentanecarboxylic acid methyl ester (100 mg,0.58 mmol) and allyl bromide (121 mg, 1 mmol) were dissolved in acetone(5ml). Potassium carbonate (138 mg, 1 mmol) was added to the solution.The mixture was heated under refluxing with stirring for 5 hours andthen was cooled and was filtered. The filtrate was concentrated under areduced pressure. The residue was purified by a silica gel columnchromatography (ethyl acetate: n-hexane=1: 4) to obtain 89 mg of1-allyl-5-cyanomethyl-2-oxo-cyclopentanecarboxylic acid methyl ester asviscous oily product. Yield: 69%. Infrared spectrum(cm⁻¹): 2235, 1755,1730, 1640, 925. NMR spectrum (CDCl₃) δ : 1.60 - 3.05 (m, 9H), 3.73 (s,3H), 4.88 - 6.07 (m, 3H).

Preparation 15

1-Allyl-5-cyanomethyl-2-oxo-cyclopentanecarboxylic acid methyl ester(220 mg, 1 mmol) and lithium iodide (2.68 mg, 2 mmol) were dissolved indimethylformamide (3 ml).

The solution was stirred at 120° C for 5 hours and was cooled and wasadmixed with an aqueous solution of ammonium chloride. The reactionproduct was extracted with ethyl acetate and the extract was washed witha saturated sodium chloride aqueous solution and was dried overanhydrous magnesium sulfate, and was filtered. The filtrate wasconcentrated under a reduced pressure and the residue was purified by asilica gel column chromatography (ethyl acetate : n-hexane=1 : 4) toobtain 90 mg of 2-allyl-3-cyanomethyl-cyclopentanone as oily product.Yield: 55%. Infrared spectrum (cm⁻¹) : 2240, 1740, 1640, 920. NMRspectrum (CDCl₃) δ : 1.60 - 3.05 (m, 10H), 4.83 - 6.07 (m, 2H).

Preparation 16

3-Cyanomethyl-2-(cis-2'-pentenyl)-cyclopentanone (220 mg, 1.15 mmol) wasdissolved in a mixture of ether (20 ml) and methanol (5 ml). Thesolution was cooled to 0° C and dry hydrogen chloride gas was fed intothe solution to saturate it and the solution was kept for one night.

Argon gas was passed through the solution to remove excess hydrogenchloride. The reaction mixture was poured on 50 g of ice and was stirredfor 30 minutes. Sodium chloride was added to the water phase and thereaction product was extracted with ethyl acetate. The extract waswashed with a saturated sodium chloride aqueous solution and then, wasdried over anhydrous magnesium sulfate and was filtrated. The solventwas distilled off under a reduced pressure and the residue was purifiedby a silica gel column chromatography (ethyl acetate: n-hexane=1 : 9) toobtain 188 mg of3-methoxycarbonylmethyl-2-(cis-2'-pentenyl)-cyclopentanone.(methyljasmonate). Yield: 73%. Infrared spectrum (cm⁻¹) : 1740, 1160. NMRspectrum (CDCl₃) δ : 0.94 (t, J=7Hz, 3H), 1.40 - 2.90 (m, 12H), 3.64 (s,3H), 5.30 (m, 2H).

Preparation 17

3-Cyanomethyl-2-(cis-2'-pentenyl)-cyclopentanone (4.0g, 21 mmol) wasdissolved in a mixture of ether (80 ml) and methanol (50 ml). Thesolution was cooled to 0° C and dried hydrogen chloride gas was fed intothe solution to saturate it. The reaction mixture was allowed to standin refrigerator for one night. Argon gas was passed through the solutionto remove excess hydrogen chloride. Then the reaction mixture wasconcentrated under a reduced pressure to remove the almost solvent used.The mixture of ether, ice and water was added to the residue. Thereaction mixture was stirred over night. Sodium chloride was added tothe water phase and the reaction product was extracted with ether andseveral times with ethyl acetate. The aqueous layer was neutralized withcold 10% aqueous sodium hydroxide and extracted with ethyl acetate. Thecombined organic layer was washed with brine and was dried overanhydrous magnesium sulfate and was filtered. The solvent was distilledoff under a reduced pressure and the residue was purified by a silicagel column chromatography (ethyl acetate : n-hexane= 1.5 : 8.5) toobtain 3.96 g of3-methoxycarbonylmethyl-2-(cis-2'-pentenyl)-cyclopentanone. (methyljasmonate). Yield: 84%. Preparation 18:

In argon atmosphere, sodium cyanide (2.16 g, 44 mmol) and2-oxo-bicyclo[3.1.0]hexane-1-carboxylic acid methyl ester (6.18 g, 40mmol) were added to dimethyl sulfoxide (40 ml). The mixture was stirredat room temperature for 24 hours and was acidified with a dilutedhydrochloric acid. The reaction product was extracted several times withethyl acetate. The combined ethyl acetate layer was washed with brineand dried over anhydrous magnesium sulfate and was concentrated to giveoily residue (7.79 g) which was mainly composed of5-cyanomethyl-2-oxo-cyclopentane carboxylic acid methyl ester. The oilyresidue obtained above and 1-bromo-2-pentyne (6.32 g, 43 mmol) weredissolved in acetone (70 ml). Potassium carbonate (5.94 g, 43 mmol) wasadded to the solution. The mixture was heated under refluxing withvigorously stirring overnight. After cooling the reaction mixture, itwas filtered through Celite layer and the filtrate was concentratedunder a reduced pressure to give the semi-solid residue (10.32 g) whichwas mainly composed of 5-cyanomethyl-2-oxo-1-(2'-pentynyl)cyclopentanecarboxylic acid methyl ester.

Then, the semi-solid residue obtained above was dissolved in dimethylsulfoxide (20 ml). Lithium iodide (5.36 g, 40 mmol) was added to thesolution with stirring and the mixture was stirred at 130° C for 3 hoursand was cooled to the room temperature. The reaction mixture wasneutralized with aqueous ammonium chloride solution and extractedseveral times with ethyl acetate. The combined organic layer was washedwith brine and dried over anhydrous magnesium sulfate and was filtered.The filtrate was concentrated under a reduced pressure to obtain theoily residue. The residue was purified by distillation to obtain 2.48 gof 3-cyanomethyl-2-(2'-pentynyl)-cyclopentanone as an oil. Yield: 33%[overall yield based on 2-oxo-bicyclo[3.1.0]-hexane-1-carboxylic acidmethyl ester] Boiling point: 135°-142° C/0.9 mmHg

Reference 1

In accordance with the process of Preparation 1, 7-octene-2,4-dione (8.4g; 60 mmol), triethylamine (6.1g; 60 mmol) and p-toluenesulfonyl azide(11.8 g; 60 mmol) were used as starting materials and the final productwas purified by silica gel column chromatography with a mixture ofethylacetate: n-hexane=1:9, to obtain 8.4 g of7-octene-3-diazo-2,4-dione as a yellow oily product. Yield: 84%.Infrared spectrum (cm⁻¹); 2115, 1665; NMR spectrum (CCl₄), δ; 2.10 -2.50 (m, 2H), 2.30 (s, 3H), 2.50 - 2.90 (m, 2H), 4.63 - 5.20 (m, 2H),5.37 - 6.16 (m, 1H).

Reference 2

In accordance with the process of Preparation 2, the7-octene-3-diazo-2,4-dione of Reference 1 (8.17 g; 49 mmol) andanhydrous cupric sulfate (5 g) were used to obtain 2.52 of1-acetyl-2-oxo-bicyclo [3.1.0] hexane as an oily product. Yield: 37%.Boiling point: 55° - 57° C/0.15 mmHg;

Infrared spectrum (cm⁻¹); 1725, 1690; NMR spectrum (CCl₄)δ: 1.37 (dd, J= 4 Hz, J = 6 Hz, 1H), 1.76 - 2.70 (m, 6H), 2.40 (s, 3H).

What is claimed is:
 1. A method for producing a fragrant3-cyanomethylcyclopentanone jasmonoide intermediate having the formula:##STR7## which comprises: reacting a bicyclo[3,1,0] hexane derivativehaving the formula: ##STR8## wherein R³ represents alkoxy or alkyl, witha cyanating agent selected from the group consisting of hydrogencyanide, acetone cyanohydrin and metal cyanides under basic conditionsin an inert solvent; andeliminating said ##STR9## group when said R³ isalkoxy, by first hydrolyzing said cyanated hexane derivative and thendecarboxylating said hydrolyzed hexane derivative or by heating saidcyanated hexane derivative in the presence of an alkali metal salt whensaid R³ group is alkyl.
 2. A method for producing a fragrant3-cyanomethylcyclopentanone jasmonoide intermediate having the formula:##STR10## wherein R² represents alkoxycarbonyl or acyl, which comprises:reacting a bicyclo [3,1,0] hexane derivative having the formula:##STR11## wherein R³ represents alkoxy or alkyl, with a cyanating agentselected from the group consisting of hydrogen cyanide, acetonecyanohydrin and metal cyanides under basic conditions in an inertsolvent.
 3. A method for producing a fragrant3-cyanomethylcyclopentanone jasmonoide intermediate having the formula:##STR12## wherein R¹ represents alkyl, alkenyl or alkynyl and R²represents alkoxycarbonyl or acyl, which comprises:reacting a bicyclo[3,1,0] hexane derivative having the formula: ##STR13## wherein R³represents alkoxy or alkyl, with a cyanating agent selected from thegroup consisting of hydrogen cyanide, acetone cyanohydrin and metalcyanides under basic conditions in an inert solvent; and alkylating saidcyanated hexane derivative with an alkylating agent of the formula R¹ Z,wherein R¹ is alkyl, alkenyl or alkynyl and Z is halogen, or acyloxyunder basic conditions in a solvent.
 4. A method for producing afragrant 3-cyanomethylcyclopentanone jasmonoide intermediate having theformula: ##STR14## wherein R' represents alkyl, alkenyl, or alkynyl,which comprises: reacting a bicyclo[3,1,0] hexane derivative having theformula: ##STR15## wherein R³ represents alkoxy or alkyl, with acyanating agent selected from the group consisting of hydrogen cyanide,acetone cyanohydrin and metal cyanides under basic conditions in aninert solvent;alkylating said cyanated hexane derivative with analkylating agent of the formula R¹ Z, wherein R¹ is alkyl, alkenyl oralkynyl and Z is halogen, or acyloxy under basic conditions in asolvent; and eliminating said ##STR16## group when said R³ is alkoxy, byfirst hydrolyzing said cyanated hexane derivative and thendecarboxylating said hydrolyzed hexane derivative or by heating saidcyanated hexane derivative in the presence of an alkali metal salt whensaid R³ group is alkyl.
 5. The method of claim 3, wherein said acyloxygroup of group Z is tosyloxy.
 6. The method of claim 4, wherein saidacyloxy group of group Z is tosyloxy.